Published online Jul 26, 2026. doi: 10.4330/wjc.v18.i7.120097
Revised: March 13, 2026
Accepted: May 28, 2026
Published online: July 26, 2026
Processing time: 155 Days and 21.7 Hours
As a crucial pathological event during sepsis progression, atrial electrical re
To investigate the effects and mechanisms of the ultrashort-acting β-blocker landiolol on atrial electrical and structural remodeling in septic rats.
A rat model of sepsis was established. The effects of landiolol on right atrial conduction time, conduction velocity, conduction dispersion, and basic electrophysiological parameters (PR interval, heart rate) were assessed using electrical mapping technology. Myocardial inflammatory injury was observed via hematoxylin and eosin staining, serum levels of inflammatory cytokines were measured by enzyme-linked immunosorbent assay, and myocardial fibrosis was evaluated using Masson staining. Apoptosis and endoplasmic reticulum stress-related proteins: Glucose-regulated protein 78 and C/EBP homologous protein were detected by immunofluorescence, immunohistochemistry, and Western blot. The expression of calumenin was examined by immunohistochemistry and Western blot.
Landiolol partially ameliorated sepsis-induced prolongation of atrial conduction time, decreased conduction velocity, increased conduction dispersion, and altered PR interval. Landiolol significantly attenuated myocardial inflammatory cell infiltration, necrosis, and elevated serum levels of tumor necrosis factor-α and interleukin-6 induced by sepsis. It also improved collagen deposition and fibrosis in the myocardium and reduced endoplasmic reticulum stress-induced apoptosis. Furthermore, landiolol significantly upregulated the expression of calumenin protein.
Landiolol may protect myocardium by upregulating calumenin expression, thereby alleviating electrical and structural remodeling in septic rats. This study provides evidence for the use of landiolol in alleviating atrial re
Core Tip: This study first established a sepsis rat model and validated the modeling success by detecting elevated serum inflammatory cytokine levels using enzyme-linked immunosorbent assay. The model was treated with landiolol to compare the degree of inflammatory injury, myocardial fibrosis, and changes in atrial electrophysiology among the different groups. Immunofluorescence, immunohistochemistry, and Western blot analyses were performed to detect the expression of apoptosis-related proteins and endoplasmic reticulum stress-related proteins (glucose-regulated protein 78 and C/EBP homologous protein) and calumenin. The results indicated that landiolol may protect the myocardium by upregulating calumenin expression, thereby mitigating atrial electrical and structural remodeling in sepsis rats.
- Citation: He ZH, Wu LK, Liu H, Bai LY, Du JJ, Ma KY, Wang Y, Zhao M. Landiolol attenuates atrial remodeling in septic rats by upregulating calumenin. World J Cardiol 2026; 18(7): 120097
- URL: https://www.wjgnet.com/1949-8462/full/v18/i7/120097.htm
- DOI: https://dx.doi.org/10.4330/wjc.v18.i7.120097
Sepsis, a systemic inflammatory response syndrome triggered by infection, has seen a continuous rise in global incidence and has become a major public health issue requiring urgent resolution[1]. Not only does it lead to overactivation of the body’s immune system, triggering a systemic inflammatory cascade, but it also causes damage to multiple vital organs, resulting in Multiple Organ Dysfunction Syndrome. It has reported that 30%-60% of patients with sepsis experience myocardial depression, known as sepsis-induced cardiomyopathy[2]. Patients with sepsis-induced cardiomyopathy are accompanied by various cardiac-related complications, among which sepsis-associated atrial fibrillation (SA-AF) stands out as particularly prominent. SA-AF has extremely high mortality and disability rates, severely impacting patients’ survival and health[3]. Meanwhile, studies have found that the incidence of SA-AF is relatively high among patients with sepsis, indicating clinical deterioration and a high risk of death. Once SA-AF occurs, it significantly increases the mortality rate in the intensive care unit[4]. After the occurrence of SA-AF in patients, their hospital stay is significantly prolonged, their medical costs increase sharply, and their quality of life declines. Currently, the underlying mechanisms of SA-AF remain unclear, treatment options are limited, and conventional approaches often fail to achieve satisfactory outcomes, resulting in a generally poor prognosis for affected patients[5,6].
The pathogenesis of SA-AF is complex, and is believed to be associated with atrial electrical and structural remodeling[7].
The features of atrial electrical remodeling are manifested as a shortening of the atrial effective refractory period and an increased susceptibility to AF induction[8]. Atrial structural remodeling tissue fibrosis, and cellular apoptosis, serves as a critical foundation for the development of AF[9]. Dilation of the atrial chamber is a key factor in sustaining reentry circuits, while fibrosis disrupts the continuity of myocardial fiber bundles. It leads to localized conduction block and thereby promoting the onset of AF. However, the underlying mechanisms of these remodeling phenomena require further studied.
As the Cab45/reticulocalbin/ERC-45/calumenin family, calumenin was found in the endoplasmic reticulum/sarcoplasmic reticulum of mammalian cardiomyocytes. Its structure contains multiple (E helix and F helix) EF-hand motifs, enabling it to bind calcium ions (Ca2+)[10]. Calumenin interacts with the Ryanodine receptor channel and Ca2+-ATPase (specifically SERCA2a) within cardiomyocytes, regulating calcium release, reuptake, and storage processes. Through these interactions, it plays a cooperative role in maintaining the stability of intracellular calcium cycling[11]. Previous studies by our team have demonstrated that calumenin alleviates endoplasmic reticulum stress (ERS) in cardiomyocytes and reduces ERS-mediated apoptosis[2]. Furthermore, atrial tissue from patients with AF showed significantly reduced expression of calumenin, accompanied by increased expression of the ERS chaperone glucose-regulated protein 78 (GRP78) and the pro-apoptotic factor C/EBP homologous protein (CHOP)[1,12]. Silencing calu
Landiolol is a novel ultrashort-acting β-blocker with a unique pharmacological profile[16]. Its β-blocking effect rapidly reduces sympathetic nerve activity and decreases catecholamine-induced cardiac stimulation, thereby lowering heart rate (HR) and blood pressure, and reducing cardiac workload. Beyond its β-adrenergic blockade, landiolol also exhibits potential anti-inflammatory and antioxidant properties. Some reported has found that landiolol inhibit the release of inflammatory mediators. As same time, it reduces the production of oxidative stress products and protecting cardiac cells from oxidative injury. Landiolol has demonstrated significant protective effects in cardiovascular diseases[17,18]. These have confirmed that landiolol improve myocardial perfusion, reduce infarct size, and decrease the incidence of arrhythmias in patients with acute myocardial infarction. In heart failure, it has been shown to enhance cardiac function, improve quality of life, and increase survival rates[19,20]. Although current research on landiolol of AF is limited, existing studies suggest that landiolol may help prevent and treat this condition by suppressing sympathetic nerve activity and reducing atrial electrophysiological instability[21]. However, the role of landiolol in SA-AF has not been investigated. Atrial electrical and structural remodeling is the core pathological mechanism and necessary precursor for the occurrence and maintenance of AF, and the abnormal electrophysiological characteristics and structural damage observed in remodeling are the direct basis for AF induction. In our research, we studied the targets and signaling pathways of landiolol treatment with SA-AF and explore the regulatory mechanisms of landiolol on calumenin, thereby opening new avenues for future research.
Thirty-two Sprague-Dawley rats (6-8 weeks old) weighing 200 ± 20 g were selected and maintained under specific pathogen-free conditions. The animals were housed in a controlled environment with free access to food and water. Sepsis was induced using the cecal ligation and puncture method. All rats are randomly divided into control group (n = 12), sepsis group (n = 12), sepsis + landiolol group (n = 8). For the control group and sepsis group, the four animals of each group were only used for mapping experiments. The sham-operated group (Sham group) underwent the same surgical procedure including laparotomy and cecal manipulation but without ligation or puncture. All animal in these experiments were conducted in accordance with ethical guidelines for laboratory animal welfare and were approved by the Medical Ethics Committee of Affiliated Hospital of Inner Mongolia Minzu University (approval No. NM-LL-2024-04-01-36).
A sepsis model was set up and the effects of different doses of landiolol (Nanjing Haichen Pharmaceutical Co., Ltd, Nanjing, Jiangsu Province, China) (drug 1: 0.1 mg; drug 2: 0.2 mg; drug 3: 0.4 mg) was investigated on atrial electrical conduction. Our study aimed to evaluate the electrophysiological effects of landiolol on atrial cardiomyocytes in septic rats (Figure 1).
Rat serum cytokine levels were measured according to the enzyme-linked immunosorbent assay kit instructions. The optical density of each well was then read at 450 nm using a microplate reader. A standard curve was generated from the optical density values of the standards, and the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in rat serum were calculated accordingly (Shanghai Lengton Biotechnology Co., Ltd, Shanghai, China).
Rats in each group were anesthetized and then euthanized. The hearts were carefully removed and intact cardiac tissue was collected. Heart tissue sections were fixed in paraffin, cut into slices, and then stained with hematoxylin and eosin (HE) as well as Masson’s trichrome. A microscope imaging system was used to look at and compare the tissue damage, including eosinophil and neutrophil buildup and collagen fiber deposition around blood vessels and in the spaces between heart muscle cells.
Heart tissue samples were fixed in 4% paraformaldehyde. After fixation, the tissues were routinely dewaxed and rehydrated. Antigen retrieval was done using microwave heating. The sections were treated with 3% hydrogen peroxide to block endogenous peroxidase activity. Then the sections were incubated with primary antibody, and then secondary antibody. Color development was carried out with 3,3’-diaminobenzidine. The reaction was stopped with distilled water as soon as the staining looked good. Counterstaining was done with hematoxylin. The sections were then dehydrated in graded alcohols and mounted with neutral resin. We looked at the sections under a microscope to see positive staining of inflammatory cells in the tissue. Images were taken and then analyzed with ImageJ software for quantification.
After protein extraction, the samples were separated by 10% SDS-PAGE (Beijing Solarbio Science & Technology Co., Ltd, Beijing, China). The membrane was then incubated with primary antibodies against calumenin, GRP78, and CHOP (Suzhou Bering Biotechnology Co., Ltd, Suzhou, Jiangsu Province, China). Subsequently, the membrane was incubated with a secondary antibody diluted 1:4000 in 1% bovine serum albumin. Protein bands were visualized using an enhanced chemiluminescence detection system, and grayscale values were quantified using ImageJ software.
Experimental data were texted as mean ± SD, and analyzed using SPSS 26.0 statistical software. One-way analysis of variance was employed to assess statistical differences between groups. For pairwise comparisons between groups, the least significant difference test was used for analysis. A P value < 0.05 was considered statistically significant.
In this study, electrophysiological mapping technology was adopted to investigate the effects of landiolol on the right atrial conduction time and conduction velocity (CV) in a rat model of sepsis. In terms of conduction time, the control group maintained stable performance. The sepsis model group exhibited a significant prolongation of conduction time. It suggested that sepsis exerts an adverse impact on atrial conduction. After intervention with different doses of landiolol, the conduction time changed to varying degrees. It showed a complex dose-response relationship. The low-dose group exhibited prolonged conduction time compared to the model group, potentially attributable to an initial high-dose effect. In contrast, the medium-dose group showed shortened conduction time relative to the model group. It indicated a beneficial effect at this dosage. The high-dose group showed further prolongation with considerable variability. After drug washout, the conduction time was significantly shortened and approached the level of the control group, indicating that the effect of landiolol was reversible. In terms of CV, values remained stable in the control group. CV was markedly decreased in the sepsis model group. Administration of landiolol further reduced CV in most dose groups. Partial recovery of CV was observed after drug washout. These results suggest that landiolol exerts dose-dependent and reversible effects on atrial conduction time and CV in septic rats (Figure 2).
Subsequently, the effect of landiolol on right atrial conduction heterogeneity in septic rats was evaluated (Figure 3). The control group exhibited low conduction heterogeneity, indicating stable electrical conduction. In contrast, the sepsis model group showed a significant increase in conduction heterogeneity. It suggested impaired conduction stability and disrupted synchrony of atrial electrical activity induced by sepsis. After administration of different doses of landiolol, conduction heterogeneity was further elevated in all treatment groups compared with the model group, with the most pronounced effect observed in the high-dose group, indicating that a higher dose may aggravate electrical instability. Following drug washout, conduction heterogeneity decreased slightly but remained higher than that in the control group. It suggested that landiolol exerted a residual effect on conduction dispersion even after drug elimination.
In terms of PR interval, the control group kept its measurements steady throughout the experiment. The sepsis model group presented an obvious shortening of the PR interval, which reflected that sepsis could interfere with atrioventricular conduction. After landiolol administration, the PR interval was further shortened in the 0.1 mg/minute and 0.2 mg/minute subgroups. By comparison, the 0.4 mg/minute group displayed an unexpected prolongation, which might be attributed to a unique pharmacological response at this relatively high dose. Following drug washout, the PR interval partially recovered. In terms of HR, the control group remained at a consistent level. The model group showed a slight decrease in HR. Under landiolol treatment, the 0.1 mg/minute and 0.2 mg/minute groups demonstrated a significant reduction in HR. But the 0.4 mg/minute group exhibited a return to levels close to the control group. Following drug washout, partial recovery of HR was also observed. These findings indicate that landiolol exerts complex, dose-dependent effects on both PR interval and HR in septic rats (Figure 3C and D).
HE staining of rat myocardial tissue sections revealed significant pathological changes in the sepsis group, including disorganized myocardial fiber arrangement, localized edema and necrosis of cardiomyocytes, and extensive inflammatory cell infiltration in the interstitium, indicating severe inflammatory damage induced by sepsis. Following landiolol intervention, the pathological damage in myocardial tissue was notably alleviated (Figure 4A). Simultaneously, the results of Masson’s trichrome staining demonstrated that landiolol ameliorated collagen deposition and reduced myocardial fibrosis levels in septic rats (Figure 4B). Enzyme-linked immunosorbent assay results demonstrated that landiolol reduced the expression levels of TNF-α and IL-6 in the serum of septic rats (Figure 4C and D).
To determine the cellular consequences of landiolol on cardiomyocytes apoptosis, we performed a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The numbers of transferase dUTP nick end labeling positive cells were increased in sepsis (Figure 5A). Landiolol inhibited apoptosis (Figure 5A). Immunohistochemistry and Western blot analysis showed that GRP78 and CHOP were markedly increased in hearts of the sepsis group compared with the control group; however, GRP78 and CHOP were significantly decreased following treatment with landiolol (Figure 5B-H).
Calumenin expression in rat atrial muscle tissue was detected using immunohistochemical staining combined with Western blot assay. The expression levels of calumenin in hearts of the sepsis group were decreased compared with the control group; however, the levels were markedly increased following treatment with landiolol (Figure 6).
As a systemic inflammatory response syndrome triggered by infection, sepsis often leads to Multiple Organ Dysfunction Syndrome, with cardiovascular system involvement being particularly common and severe[22-24]. Among these complications, SA-AF is a serious condition that severely threatens patients’ lives and health due to its high mortality and disability rates[25]. This study focuses on the impact of landiolol on atrial remodeling in septic rats. Utilizing techniques such as electrical mapping, pathological staining, and Western blot analysis, we thoroughly investigate the mechanism of action of landiolol and demonstrate its effects on atrial structural remodeling in septic rats. This research aims to provide an in-depth exploration of landiolol’s mechanisms.
As an ultrashort-acting β-blocker, landiolol primarily functions by rapidly reducing sympathetic nerve activity. The body enters a state of stress characterized by abnormally heightened sympathetic excitability and excessive catecholamine release in sepsis. These catecholamines bind to β-receptors on the cardiomyocyte membrane, activating a series of intracellular signaling pathways that lead to dysfunction of ion channels[26].
This study conducted electrical mapping of the atria in septic rats. Compared to the control group, the overall CV in the atria of the septic Sprague-Dawley rats was slower, with increased heterogeneity, which is consistent with previous reports[6]. These findings suggest that this may be due to bacterial-induced inflammation causing a significant reduction in sodium current density, slowing the upstroke velocity of the action potential phase 0, inhibiting the expression of Cx40 and Cx43 proteins, leading to their distribution disorder, reduced gap junction conduction efficiency, prolonged atrial action potential duration, increased dispersion of repolarization, and elevated inflammatory factors TNF-α and IL-6, which directly inhibit atrial electrical conduction. Landiolol, as a highly selective β1-receptor blocker, and inhibits the calcium current in cardiomyocytes. This reduced activity indirectly slows the CV of electrical signals between atrial myocytes and prolongs conduction time. Short-term use of this drug can exacerbate the decline in gap junction communication efficiency, further weakening the synchrony of atrial electrical conduction. Sepsis itself leads to slowed atrial conduction. Landiolol, by suppressing the compensatory sympathetic excitation, removes this compensation after blockade, making the conduction delay more pronounced. While landiolol reduces myocardial calcium overload, it also diminishes calcium-dependent synergy in electrical signal conduction, exacerbating the conduction slowing. We conclude that landiolol may promote further electrical remodeling in the atria of septic rats, leading to a further decrease in CV and an increase in conduction anisotropy, potentially promoting the occurrence of AF. Clinically, the purpose of using landiolol for sepsis complicated by AF is to reduce atrioventricular conduction, lower the ventricular rate to protect cardiac function, and simultaneously inhibit catecholamine-induced ventricular arrhythmias. Therefore, it is concluded that landiolol may not have a rhythm-converting effect on AF complicating sepsis, which is a key distinction from the application of class III antiarrhythmic drugs.
Current approaches to managing sepsis-induced cardiac electrophysiological abnormalities often rely on traditional antiarrhythmic drugs, such as amiodarone and propafenone[27]. These agents primarily function by directly targeting ion channels to alter transmembrane ion flow, thereby modulating electrical activity[28]. However, in the complex pathological environment of sepsis, strategies focusing solely on ion channel modulation often yield limited therapeutic benefits.
In this study, HE and Masson staining revealed that landiolol significantly alleviated myocardial tissue injury and fibrosis in rats with sepsis-induced cardiomyopathy. The systemic inflammatory response triggered by sepsis is a critical factor contributing to atrial structural remodeling[29]. Inflammatory mediators, including TNF-α and IL-6, are extensively released during sepsis[30]. These cytokines directly damage cardiomyocytes, leading to cellular swelling, degeneration, and even necrosis. Furthermore, they activate inflammatory signaling pathways, such as the nuclear factor-kappa B pathway, promoting fibroblast proliferation and collagen deposition, which ultimately results in atrial fibrosis[31]. The study identified that landiolol exhibits potential anti-inflammatory properties. It may contribute to its protective effects against sepsis-induced atrial structural and electrical remodeling.
Calumenin is a calcium-binding protein located in the endoplasmic reticulum/sarcoplasmic reticulum of mammalian cardiomyocytes[32]. It is closely associated with calcium release, reuptake, and storage in cardiomyocytes, playing a critical role in maintaining calcium cycling homeostasis[33]. Additionally, it regulates ERS-induced apoptosis[14]. During sepsis, the expression of calumenin decreases or its degradation increases, leading to calcium overload in cardiomyocytes. Calcium overload activates the ERS response, upregulating the expression of the ERS chaperone protein GRP78 while simultaneously activating apoptotic signaling pathways, promoting increased expression of the apoptotic factor CHOP, ultimately resulting in cardiomyocyte apoptosis. In our study, the sepsis model group exhibited reduced calumenin levels and upregulation of GRP78 and CHOP, triggering ERS and apoptosis. In contrast, the sepsis + landiolol group showed recovery of calumenin levels and reduction of GRP78 and CHOP, indicating that landiolol inhibits ERS and the apoptosis it induces.
Landiolol may not have a rhythm-converting effect on AF complicating sepsis. The clinical application of landiolol in treating AF is to reduce atrioventricular conduction, thereby inhibiting the occurrence of ventricular fibrillation. However, landiolol can ameliorate atrial structural remodeling. These findings provide a novel theoretical foundation and a potential therapeutic strategy for alleviating atrial remodeling (the pathological basis of SA-AF). Due to the lack of an in vivo AF induction protocol in this study, the direct effect of landiolol on the induction and suppression of SA-AF needs to be further verified in subsequent experiments with AF induction models. Another limitation of this study is the lack of genetic or pharmacological interventions targeting calumenin. In future research, experiments involving siRNA-mediated silencing or CRISPR/Cas9-based technology to knockout calumenin in cardiac cells are required to confirm whether the protective effects of landiolol are indeed dependent on calumenin. Despite this limitation, our findings identify calumenin as a downstream effector molecule of landiolol, which provides a novel direction for the treatment of SA-AF.
Thanks to our friends for our support.
| 1. | Chiu C, Legrand M. Epidemiology of sepsis and septic shock. Curr Opin Anaesthesiol. 2021;34:71-76. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 193] [Cited by in RCA: 163] [Article Influence: 32.6] [Reference Citation Analysis (1)] |
| 2. | Hollenberg SM, Singer M. Pathophysiology of sepsis-induced cardiomyopathy. Nat Rev Cardiol. 2021;18:424-434. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 110] [Cited by in RCA: 530] [Article Influence: 106.0] [Reference Citation Analysis (0)] |
| 3. | Goss CH, Carson SS. Is severe sepsis associated with new-onset atrial fibrillation and stroke? JAMA. 2011;306:2264-2266. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 3] [Cited by in RCA: 6] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
| 4. | Tamazyan V, Khachatryan A, Batikyan A, Harutyunyan H, Aryal B, Achuthanandan S, Hollander G. Sepsis-induced Atrial Fibrillation: Can We Predict and Prevent This High-Risk Complication? Cureus. 2025;17:e85387. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 3] [Cited by in RCA: 3] [Article Influence: 3.0] [Reference Citation Analysis (0)] |
| 5. | Li J, Wang S, Ma C, Ning N, Huang Y, Jiao M, Zhang J, Sun W, Li J, Zhao B, Mao E, Che Z, Gao C. Sepsis-Induced Coagulopathy Score is Associated with an Increased Risk of New-Onset Atrial Fibrillation in Septic Patients: A Two-Centered Retrospective Study. J Inflamm Res. 2024;17:5889-5899. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 4] [Reference Citation Analysis (0)] |
| 6. | Xiang J, Cao J, Wang X, Shao S, Huang J, Zhang L, Tang B. Neutrophil extracellular traps and neutrophil extracellular traps-related genes are involved in new-onset atrial fibrillation in LPS-induced sepsis. Int Immunopharmacol. 2024;138:112550. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 21] [Reference Citation Analysis (0)] |
| 7. | Allessie M, Ausma J, Schotten U. Electrical, contractile and structural remodeling during atrial fibrillation. Cardiovasc Res. 2002;54:230-246. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 1141] [Cited by in RCA: 1035] [Article Influence: 43.1] [Reference Citation Analysis (0)] |
| 8. | Zhong S, He R, Yu J, Zhao H. Subcutaneous BNP Injections in Rabbits: A Novel Approach to Mitigate Myocardial Remodeling in Atrial Fibrillation. Discov Med. 2024;36:2182-2190. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 2] [Reference Citation Analysis (0)] |
| 9. | Hu YF, Chen YJ, Lin YJ, Chen SA. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol. 2015;12:230-243. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 944] [Cited by in RCA: 876] [Article Influence: 79.6] [Reference Citation Analysis (0)] |
| 10. | Lee JH, Kwon EJ, Kim DH. Calumenin has a role in the alleviation of ER stress in neonatal rat cardiomyocytes. Biochem Biophys Res Commun. 2013;439:327-332. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 59] [Cited by in RCA: 57] [Article Influence: 4.4] [Reference Citation Analysis (0)] |
| 11. | Sahoo SK, Kim DH. Characterization of calumenin in mouse heart. BMB Rep. 2010;43:158-163. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 35] [Cited by in RCA: 36] [Article Influence: 2.3] [Reference Citation Analysis (0)] |
| 12. | Jha AK. Heart rate control in septic shock with tachycardia. Intensive Care Med. 2025;51:217-218. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 1] [Reference Citation Analysis (0)] |
| 13. | Wang Y, Wang YL, Huang X, Yang Y, Zhao YJ, Wei CX, Zhao M. Ibutilide protects against cardiomyocytes injury via inhibiting endoplasmic reticulum and mitochondrial stress pathways. Heart Vessels. 2017;32:208-215. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 7] [Cited by in RCA: 14] [Article Influence: 1.4] [Reference Citation Analysis (0)] |
| 14. | Wang Y, Xuan L, Cui X, Wang Y, Chen S, Wei C, Zhao M. Ibutilide treatment protects against ER stress induced apoptosis by regulating calumenin expression in tunicamycin treated cardiomyocytes. PLoS One. 2017;12:e0173469. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 10] [Cited by in RCA: 16] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
| 15. | Li X, Zhang DQ, Wang X, Zhang Q, Qian L, Song R, Zhao X, Li X. Irisin alleviates high glucose-induced hypertrophy in H9c2 cardiomyoblasts by inhibiting endoplasmic reticulum stress. Peptides. 2022;152:170774. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 2] [Cited by in RCA: 15] [Article Influence: 3.8] [Reference Citation Analysis (0)] |
| 16. | Bezati S, Boultadakis A, Ventoulis I, Polyzogopoulou E, Parissis JT. Optimal use of intravenous landiolol in acute cardiac care. Expert Rev Cardiovasc Ther. 2023;21:855-866. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 4] [Cited by in RCA: 5] [Article Influence: 1.7] [Reference Citation Analysis (0)] |
| 17. | Yasuda T, Kamiya H, Tanaka Y, Watanabe G. Ultra-short-acting cardioselective beta-blockade attenuates postischemic cardiac dysfunction in the isolated rat heart. Eur J Cardiothorac Surg. 2001;19:647-652. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 11] [Cited by in RCA: 10] [Article Influence: 0.4] [Reference Citation Analysis (0)] |
| 18. | Hoshi T, Sato A, Nishina H, Kakefuda Y, Wang Z, Noguchi Y, Aonuma K. Acute hemodynamic effects of landiolol, an ultra-short-acting beta-blocker, in patients with acute coronary syndrome: preliminary study. J Cardiol. 2012;60:252-256. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 11] [Cited by in RCA: 16] [Article Influence: 1.1] [Reference Citation Analysis (0)] |
| 19. | Kurosawa S, Kanaya N, Niiyama Y, Nakayama M, Fujita S, Namiki A. Landiolol, esmolol and propranolol protect from ischemia/reperfusion injury in isolated guinea pig hearts. Can J Anaesth. 2003;50:489-494. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 21] [Cited by in RCA: 21] [Article Influence: 0.9] [Reference Citation Analysis (0)] |
| 20. | Goyagi T, Kimura T, Nishikawa T, Tobe Y, Masaki Y. Beta-adrenoreceptor antagonists attenuate brain injury after transient focal ischemia in rats. Anesth Analg. 2006;103:658-663. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 36] [Cited by in RCA: 36] [Article Influence: 1.8] [Reference Citation Analysis (0)] |
| 21. | Ghallab M, Ahmed MS, Ostrow TH, Rasool MH, Alagha Z, Miller D, Frishman WH, Aronow WS, Frenkel D. Landiolol for Treating Arrhythmias: A State-of-The-Art Review. Cardiol Rev. 2026;34:212-217. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 4] [Cited by in RCA: 5] [Article Influence: 5.0] [Reference Citation Analysis (0)] |
| 22. | Walkey AJ, Hammill BG, Curtis LH, Benjamin EJ. Long-term outcomes following development of new-onset atrial fibrillation during sepsis. Chest. 2014;146:1187-1195. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 159] [Cited by in RCA: 215] [Article Influence: 19.5] [Reference Citation Analysis (0)] |
| 23. | Liu D, Huang SY, Sun JH, Zhang HC, Cai QL, Gao C, Li L, Cao J, Xu F, Zhou Y, Guan CX, Jin SW, Deng J, Fang XM, Jiang JX, Zeng L. Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options. Mil Med Res. 2022;9:56. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 316] [Cited by in RCA: 356] [Article Influence: 89.0] [Reference Citation Analysis (1)] |
| 24. | Pan S, Lv Z, Wang R, Shu H, Yuan S, Yu Y, Shang Y. Sepsis-Induced Brain Dysfunction: Pathogenesis, Diagnosis, and Treatment. Oxid Med Cell Longev. 2022;2022:1328729. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 121] [Cited by in RCA: 112] [Article Influence: 28.0] [Reference Citation Analysis (0)] |
| 25. | Caraballo C, Jaimes F. Organ Dysfunction in Sepsis: An Ominous Trajectory from Infection to Death. Yale J Biol Med. 2019;92:629-640. [PubMed] |
| 26. | Kakihana Y, Nishida O, Taniguchi T, Okajima M, Morimatsu H, Ogura H, Yamada Y, Nagano T, Morishima E, Matsuda N; J-Land 3S Study Group. Efficacy and safety of landiolol, an ultra-short-acting β1-selective antagonist, for treatment of sepsis-related tachyarrhythmia (J-Land 3S): a multicentre, open-label, randomised controlled trial. Lancet Respir Med. 2020;8:863-872. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 109] [Cited by in RCA: 94] [Article Influence: 15.7] [Reference Citation Analysis (0)] |
| 27. | Balik M, Matousek V, Maly M, Brozek T. Management of arrhythmia in sepsis and septic shock. Anaesthesiol Intensive Ther. 2017;49:419-429. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 12] [Cited by in RCA: 20] [Article Influence: 2.2] [Reference Citation Analysis (0)] |
| 28. | Mankad P, Kalahasty G. Antiarrhythmic Drugs: Risks and Benefits. Med Clin North Am. 2019;103:821-834. [RCA] [PubMed] [DOI] [Full Text] [Cited by in Crossref: 21] [Cited by in RCA: 41] [Article Influence: 5.9] [Reference Citation Analysis (0)] |
| 29. | Fan D, Wu R. Mechanisms of the septic heart: From inflammatory response to myocardial edema. J Mol Cell Cardiol. 2024;195:73-82. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 40] [Cited by in RCA: 35] [Article Influence: 17.5] [Reference Citation Analysis (0)] |
| 30. | Deng P, Tang N, Li L, Zou G, Xu Y, Liu Z. Diagnostic value of combined detection of IL-1β, IL-6, and TNF-α for sepsis-induced cardiomyopathy. Med Clin (Barc). 2022;158:413-417. [RCA] [PubMed] [DOI] [Full Text] [Cited by in RCA: 27] [Reference Citation Analysis (0)] |
| 31. | Yu L, Yang Y, Wang J, Bao Z, Zheng M, Wang X, Zhu Y, Wulasihan M. PDCD4 promotes inflammation/fibrosis by activating the PPARγ/NFκB pathway in mouse atrial myocytes. Mol Med Rep. 2024;30:209. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in RCA: 9] [Reference Citation Analysis (0)] |
| 32. | Wang Y, Cui X, Wang Y, Fu Y, Guo X, Long J, Wei C, Zhao M. Protective effect of miR378* on doxorubicin-induced cardiomyocyte injury via calumenin. J Cell Physiol. 2018;233:6344-6351. [RCA] [PubMed] [DOI] [Full Text] [Full Text (PDF)] [Cited by in Crossref: 20] [Cited by in RCA: 17] [Article Influence: 2.1] [Reference Citation Analysis (0)] |